Use of microsatellite instability and immunohistochemistry testing for the identification of individuals at risk for Lynch syndrome
Use of microsatellite instability and immunohistochemistry testing for the identification of individuals at risk for Lynch syndrome
复制标题
DOI：
10.1007/s10689-004-1447-6
复制
发表时间：
2005-01-01
期刊：
影响因子：
2.2
通讯作者：
Thibodeau, SN
中科院分区：
文献类型：
--
作者：
Baudhuin, LM;Burgart, LJ;Thibodeau, SN
现在普遍认识到，临床上定义为患有遗传性非息肉病性结肠癌（HNPCC）的那些患者的特定子集在涉及DNA错配修复（MMR）的几个基因中的任何一个中具有种系突变。HNPCC家族的这一重要子集现在被定义为患有Lynch综合征。大量数据表明，Lynch综合征患者的肿瘤具有由缺陷性MMR的潜在分子参与引起的特征性特征，即存在微卫星不稳定性（MSI）和通过免疫组织化学（IHC）缺乏MMR蛋白表达。因此，现在可以通过检测肿瘤的这些肿瘤相关变化来识别林奇综合征患者。MSI和IHC是一种强大的工具，可以帮助识别Lynch综合征的风险个体，并将这些病例与其他遗传基因缺陷的HNPCC病例区分开来。此外，IHC分析提供了关于MMR基因突变的有价值的线索，允许对该基因进行全面的突变分析。在这里，我们讨论了当前和历史的观点，关于肿瘤的MSI和IHC分析散发性结肠癌和林奇综合征患者。鉴于这一背景，我们还提供了一种检测策略，用于识别Lynch综合征风险患者和随后的基因检测。
It is now generally recognized that a specific subset of those patients clinically defined as having hereditary non polyposis colon cancer (HNPCC) have germline mutations in any one of several genes involved in DNA mismatch repair (MMR). This important subset of HNPCC families is now defined as having Lynch syndrome. A considerable amount of data has shown that tumors from patients with Lynch syndrome have characteristic features resulting from the underlying molecular involvement of defective MMR, that is, the presence of microsatellite instability (MSI) and the absence of MMR protein expression by immunohistochemistry (IHC). As a result, identifying patients with Lynch syndrome can now be accomplished by testing tumors for these tumor-related changes. Together, MSI and IHC are powerful tools that help identify individuals at risk for having Lynch syndrome and to distinguish these cases from HNPCC cases with other hereditary gene defects. Furthermore, IHC analysis provides valuable clues as to which MMR gene is mutated, allowing for comprehensive mutational analyses of that gene. Here, we discuss the current and historical perspectives regarding MSI and IHC analyses in tumors from sporadic colon cancer and from patients with Lynch syndrome. Given this background, we also provide a testing strategy for the identification of patients at risk for Lynch syndrome and subsequent gene testing.